Zinc alleviates high fat diet-induced spermatogenic dysfunction in Wistar rats: role of oxidative stress, HMGB1 and inflammasome

Rev Int Androl. 2024 Mar;22(1):44-52. doi: 10.22514/j.androl.2024.007. Epub 2024 Mar 30.

Abstract

Whether chronic inflammation in the genital tract induced by obesity shares in spermatogenic dysfunction is not clearly known. We aimed to study the effect of high fat diet (HFD) on spermatogenesis, seminal oxidative stress (malondialdehyde (MDA)) and inflammatory markers (high mobility group box 1 (HMGB1), nucleotide-binding oligomerization domain, leucine rich repeat and pyrin-3 domain containing (NLRP3)) in the rat testes and the role of zinc on testicular dysfunction and chronic inflammation in high fat diet (HFD) fed rat testes. This parallel group comparative experimental study included 36 male wistar rats divided into 3 groups: group A (fed on normal control diet); group B (fed on high fat diet (HFD) only); and group C (fed on HFD with zinc supplementation 3.2 mg/kg/day orally). At the end of the 12th week, sperm count, viability and motility were assessed by computer-assisted seemen analysis (CASA), seminal malondialdehyde measured by calorimetry and histopathological examination of testicular sections was done. Immunohistochemical staining was done for HMGB1 and NLRP3 evaluation. Sperm count was lowest in group B. Groups A and C showed statistically significant higher mean sperm vitality, total and progressive motility scores (p < 0.001), while no difference was found between the groups A and C (p > 0.05). Seminal malondialdehyde level was significantly highest in group B. Tubular diameter, epithelial height and Johnsen score were significantly lowest in group B. Significantly higher HMGB1 and NLRP3 levels were demonstrated in group B (p < 0.001). Obesity is associated with testicular dysfunction, testicular oxidative stress and increased testicular HMGB1 and NLRP3. We suggest a beneficial effect of zinc on testicular function in HFD-rats.

Keywords: HMGB1; Inflammasome; Male infertility; Obesity; Oxidative stress; Zinc.

MeSH terms

  • Animals
  • Diet, High-Fat* / adverse effects
  • HMGB1 Protein* / metabolism
  • Inflammasomes* / metabolism
  • Inflammation / etiology
  • Inflammation / metabolism
  • Male
  • Malondialdehyde / analysis
  • Malondialdehyde / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Obesity / metabolism
  • Oxidative Stress* / drug effects
  • Rats
  • Rats, Wistar*
  • Sperm Count
  • Sperm Motility / drug effects
  • Spermatogenesis* / drug effects
  • Spermatozoa / drug effects
  • Testis* / drug effects
  • Testis* / metabolism
  • Zinc* / administration & dosage

Substances

  • HMGB1 Protein
  • Zinc
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Hbp1 protein, rat
  • Malondialdehyde
  • Nlrp3 protein, rat